Pien Tze Huang inhibits hypoxia-induced epithelial-mesenchymal transition in human colon carcinoma cells through suppression of the HIF-1 pathway.
Pien Tze Huang inhibits hypoxia-induced epithelial-mesenchymal transition in human colon carcinoma cells through suppression of the HIF-1 pathway.
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片仔癀通过抑制 HIF-1 通路抑制缺氧诱导的人结肠癌细胞上皮间质转化
DOI：
10.3892/etm.2014.1549
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发表时间：
2014-05
影响因子：
2.7
通讯作者：
Peng J
中科院分区：
文献类型：
--
作者：
Chen H;Shen A;Zhang Y;Chen Y;Lin J;Lin W;Sferra T;Peng J
低氧诱导的低氧诱导因子1 （HIF-1）信号通路的激活在实体肿瘤中经常观察到，并且与许多病理生理过程密切相关，包括诱导上皮-间质转化（EMT），导致癌症的进展和转移。因此，通过抑制HIF-1途径抑制EMT可能是一种很有前景的抗癌化疗策略。片仔癀（PZH）是一种历史悠久的中药，已有450多年的历史，几个世纪以来一直用于临床治疗各种类型的人类癌症。我们之前报道过PZH抑制多种细胞内信号通路，从而促进癌细胞凋亡，抑制细胞增殖和肿瘤血管生成。为了进一步探讨PZH抗肿瘤作用的机制，本研究在缺氧条件下培养HCT-8人结肠癌细胞，评估PZH对缺氧诱导的EMT的影响。缺氧可诱导HCT-8细胞emt相关的形态学改变，包括细胞粘附丧失和梭形成纤维样形态的形成。此外，缺氧可降低上皮标志物E-cadherin的表达，但增加间质标志物N-cadherin的表达。此外，缺氧显著增强HCT-8细胞的迁移和侵袭，诱导HIF-1通路的激活。然而，PZH处理HCT-8细胞可显著抑制缺氧介导的EMT和HIF-1信号。这些发现提示PZH通过抑制HIF-1通路抑制缺氧诱导的癌症EMT，这可能是PZH发挥其抗肿瘤活性的分子机制之一。
Hypoxia-induced activation of the hypoxia-inducible factor 1 (HIF-1) signaling pathway is frequently observed in solid tumors and is strongly associated with numerous pathophysiological processes, including the induction of epithelial-mesenchymal transition (EMT), which result in cancer progression and metastasis. Thus, inhibiting EMT through the suppression of the HIF-1 pathway may be a promising strategy for anticancer chemotherapy. Pien Tze Huang (PZH), a well-established traditional Chinese medicine has been prescribed for >450 years and has been used for centuries to clinically treat various types of human cancer. We previously reported that PZH suppresses multiple intracellular signaling pathways and thereby promotes the apoptosis of cancer cells and the inhibition of cell proliferation and tumor angiogenesis. In the present study, to further explore the mechanisms underlying the antitumor action of PZH, HCT-8 human colon carcinoma cells were cultured under hypoxic conditions and the effect of PZH on hypoxia-induced EMT was assessed. Hypoxia was found to induce EMT-associated morphological changes in HCT-8 cells, including loss of cell adhesion and the development of spindle-shaped fibroblastoid-like morphology. In addition, hypoxia was observed to reduce the expression of the epithelial marker E-cadherin, but increase that of the mesenchymal marker N-cadherin. In addition, hypoxia significantly enhanced HCT-8 cell migration and invasion and induced the activation of the HIF-1 pathway. However, treatment of the HCT-8 cells with PZH significantly inhibited the hypoxia-mediated EMT and HIF-1 signaling. These findings suggest that PZH inhibits hypoxia-induced cancer EMT through the suppression of the HIF-1 pathway, which may be one of the molecular mechanisms by which PZH exerts its antitumor activity.
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影响因子：
64.8
作者：
Maxwell, PH;Wiesener, MS;Ratcliffe, PJ
通讯作者：
Ratcliffe, PJ
影响因子：
56.9
作者：
Ivan, M;Kondo, K;Kaelin, WG
通讯作者：
Kaelin, WG
影响因子：
10.3
作者：
Bos, R;Zhong, H;van der Wall, E
通讯作者：
van der Wall, E
片仔癀通过抑制多种细胞途径抑制结直肠癌小鼠模型中的肿瘤血管生成
影响因子：
4.2
作者：
Shen, Aling;Lin, Jiumao;Peng, Jun
通讯作者：
Peng, Jun
DOI：
10.1073/pnas.92.12.5510
发表时间：
1995-06-06
影响因子：
11.1
作者：
WANG, GL;JIANG, BH;SEMENZA, GL
通讯作者：
SEMENZA, GL